The in-hospital trauma mortality rate in South Africa remains unknown, and it is unclear whether deficits in hospital care are contributing to the high level of trauma-related mortality. All patients hospitalized because of trauma at the Department of Surgery at Grey's Hospital, Pietermaritzburg Metropolitan Trauma Service, were prospectively entered in an electronic database starting in 2013 and the data were retrospectively analyzed. The trauma service adheres to Advanced Trauma Life Support and the doctors have attended basic and advanced courses in trauma care. The primary outcome was in-hospital mortality. Of 9795 trauma admissions, 412 (4.2%) patients died during hospital care between January 2013 and January 2019. Forty-six percent died after road traffic accidents, 19% after gunshot wounds, 13% after stab wounds, and 10% after assaults. Sixteen percent were classified as avoidable deaths due to inappropriate care and resource limitations. Fifty percent died because of traumatic brain injury and 80% of them were unavoidable. In conclusion, the in-hospital trauma mortality rate at a South African trauma center using systematic trauma care is lower than that reported from other trauma centers in the world during the past 20 years. Nevertheless, 16% of death cases were assessed as avoidable if there had been better access to intensive care, dialysis, advanced respiratory care, blood for transfusion, and improvements in surgery and medical care.